Fig. 1

YEATS2 Drives Tumorigenesis via Context-Dependent Target Genes and Pathways [19, 27, 32,33,34,35]. YEATS2 has been shown to orchestrate malignancy-specific transcriptional programs by decoding distinct histone acylation marks (H3K27ac/cr) and recruiting tissue-specific coactivators. In NSCLC, it has been observed to recruit the ATAC complex to deposit H3K9ac at ribosomal gene promoters (RPS6/RPL7), thereby sustaining ribosome biogenesis. Furthermore, analysis of PDAC models reveals that YEATS2 stabilizes TAK1, thereby constitutively activating NF-κB, which in turn drives anti-apoptotic (BCL2/XIAP) and immunosuppressive (PD-L1) gene expression. In the context of HCC progression, the PI3K/AKT pathway is implicated in metabolic rewiring, while MYC amplification occurs via H3K27ac-dependent promoter activation. Cross-cancer analyses identify common oncogenic nodes (MYC, AKT) and unique microenvironmental regulators (HIF1α in PDAC hypoxia; miR-378a-5p in HNSCC). In CRC, YEATS2 responds to elevated levels of Kcr, thereby activating ETS1 and promoting cancer metastasis. The acronyms used in this text are PDAC (pancreatic ductal adenocarcinoma cells), HCC (hepatocellular carcinoma), NSCLC (non-small cell lung cancer), CRC (colorectal cancer), LUSC (lung squamous cell carcinoma), OC (ovarian cancer), and HNSCC (head and neck squamous cell carcinoma). NF-κB, Nuclear factor kappa-B; Kac, Lysine acetylation; Kcr, Lysine crotonylation. The graphic framework is adapted from Ji et al., 2023 [19], Mi et al., [27], Zeng et al., [32], Sheng et al., [33], Liao et al., [34], and Liu et al., [35]